Uterine artery pseudoaneurysm caused by hysteroscopic surgery: A case report.

BACKGROUND: We report a case of uterine artery pseudoaneurysm (UAP) occurrence during hysteroscopic endometrial polypectomy and its treatment via uterine artery embolization (UAE). CASE SUMMARY: A 48-year-old primigravid, primiparous patient was incidentally found to have an endometrial polyp during a health checkup, and underwent a hysteroscopic polypectomy at another hospital. Her cervix was dilated with a Laminken-R® device. After the Laminken-R® was withdrawn, a large amount of genital bleeding was observed. This bleeding persisted after the hysteroscopic polypectomy, and, as hemostasis became impossible, the patient was transferred to our hospital by ambulance. On arrival, transvaginal ultrasonography revealed a 3-cm hypoechoic mass with a swirling internal pulse on the right side of the uterus, and color Doppler ultrasonography showed feeder vessels penetrating the mass. Pelvic contrast-enhanced computed tomography (CT) confirmed the presence of a mass at this site, and vascular proliferation was observed within the uterine cavity. Consequently, UAP was diagnosed, and UAE was performed. The patient's postoperative course was uneventful, and 6 mo post-UAE, no recurrence of blood flow to the UAP was observed. CONCLUSION: When abnormal genital bleeding occurs during hysteroscopic surgery, ultrasonography and contrast-enhanced CT can assist in the detection of early UAPs.

Niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer: final results of a multicenter phase 2 study.

OBJECTIVE: This study evaluated the long-term safety and efficacy of niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer. METHODS: This was a follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with platinum-sensitive, relapsed ovarian cancer. Participants received niraparib (starting dose 300 mg) once daily in continuous 28-day cycles. The primary endpoint was the incidence of Grade 3 or 4 thrombocytopenia-related events (defined as the overall incidence of the MedDRA Preferred Terms "thrombocytopenia" and "platelet count decreased") occurring in the 30 days after initial administration of niraparib, and secondary endpoints included evaluation of treatment-emergent adverse events and progression-free survival. RESULTS: Nineteen patients (median age, 62 years; median body weight, 53.9 kg) were enrolled. As previously reported, the incidence of Grade 3 or 4 thrombocytopenia-related events during the first 30 days of treatment was 31.6%. At data cutoff, median (range) treatment exposure was 504.0 (56-1,054) days and mean ± standard deviation dose intensity was 154.4±77.5 mg/day. The most common treatment-emergent adverse events were nausea (n=14, 73.7%), decreased platelet count (n=12, 63.2%), decreased neutrophil count (n=11, 57.9%), anemia, vomiting, and decreased appetite (all n=9, 47.4%). One patient was diagnosed with treatment-related leukemia, which resulted in death. Median (95% confidence interval) progression-free survival was 18.0 (5.6-26.7) months. CONCLUSION: Overall, the safety profile of niraparib was considered manageable in this study population of Japanese patients with platinum-sensitive, relapsed ovarian cancer and was consistent with that observed in studies of non-Japanese patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759587.

Mid-term outcomes of laparoscopic vaginal stump­round (Kakinuma method) and stump­uterosacral (Shull method) ligament fixation for pelvic organ prolapse: A retrospective comparative study

BACKGROUND: Laparoscopic sacrocolpopexy (LSC) and robot-assisted sacrocolpopexy (RSC) using mesh are popular approaches for treating pelvic organ prolapse (POP). However, it is not uncommon that native tissue repair (NTR) should be presented as an option to patients who are expected to have extensive intraperitoneal adhesion or patients for whom LSC or RSC is difficult owing to various risk factors. Laparoscopic vaginal stump-uterosacral ligament fixation (Shull method) has been introduced as a method for NTR in case of POP. However, effective repair using this surgical procedure may not be possible in severe POPs. To solve the problems of the Shull method, we devised the laparoscopic vaginal stump-round ligament fixation (Kakinuma method) in which the vaginal stump is fixed to the uterine round ligament, a histologically strong tissue positioned anatomically higher than the uterosacral ligament. This study aimed to retrospectively and clinically compare the two methods. METHODS: Of the 78 patients who underwent surgery for POP between January 2017 and June 2022 and postoperative follow-up for at least a year, 40 patients who underwent the Shull method (Shull group) and 38 who underwent the Kakinuma method (Kakinuma group) were retrospectively analyzed. RESULTS: No significant differences were observed between the two groups in patient background variables such as mean age, parity, body mass index, and POP-Q stage. The mean operative duration and mean blood loss in the Shull group were 140.5 ± 31.7 min and 91.3 ± 96.3 ml, respectively, whereas the respective values in the Kakinuma group were 112.2 ± 25.3 min and 31.4 ± 47.7 ml, respectively. Thus, compared with the Shull group, the operative duration was significantly shorter (P < 0.001) and blood loss was significantly less (P = 0.003) in the Kakinuma group. Recurrence was observed in six patients (15.0%) in the Shull group and two patients (5.3%) in the Kakinuma group. Hence, compared with the Shull group, recurrence was significantly less in the Kakinuma group (P = 0.015). No patients experienced perioperative complications in either group. CONCLUSIONS: The results suggest that the Kakinuma method can serve as a novel and viable NTR procedure for POP.

Abnormal uterine bleeding successfully treated via ultrasound-guided microwave ablation of uterine myoma lesions: Three case reports.

BACKGROUND: Microwave endometrial ablation (MEA) is a minimally invasive treatment method for heavy menstrual bleeding. However, additional treatment is often required after recurrence of uterine myomas treated with MEA. Additionally, because this treatment ablates the endometrium, it is not indicated for patients planning to become pregnant. To overcome these issues, we devised a method for ultrasound-guided microwave ablation of uterine myoma feeder vessels. We report three patients successfully treated for heavy menstrual bleeding, secondary to uterine myoma, using our novel method. CASE SUMMARY: All patients had a favorable postoperative course, were discharged within 4 h, and experienced no complications. Further, no postoperative recurrence of heavy menstrual bleeding was noted. Our method also reduced the myoma's maximum diameter. CONCLUSION: This method does not ablate the endometrium, suggesting its potential application in patients planning to become pregnant.

Effectiveness of treating menorrhagia using microwave endometrial ablation at a frequency of 2.45 GHz.

BACKGROUND: Microwave endometrial ablation (MEA) is a minimally invasive treatment for menorrhagia. It has been covered by the national insurance in Japan since April 2012, and its demand has been increasing as the importance of women's health has advanced in society. AIM: To examine the efficacy of MEA as a treatment option for menorrhagia. METHODS: In this study, we retrospectively analyzed 76 patients who underwent MEA between January 2016 and March 2020 in our department. MEA was performed in the lithotomy position, under general anesthesia, and with transabdominal ultrasound guidance, including the entire endometrial circumference while confirming endometrial coagulation. The Microtaze AFM-712 and the Sounding Applicator CSA-40CBL-1006200C were used for MEA, and the endometrium was ablated using a Microtaze output of 70 W and coagulation energization time of 50 s per cycle. The visual analog scale (VAS) was used to evaluate menorrhagia, menstrual pain, and treatment satisfaction. Additionally, the hemoglobin (Hb) levels before and after MEA and associated complications were investigated. RESULTS: The average age of the patients was 44.8 ± 4.0 years. While 14 patients had functional menorrhagia, 62 had organic menorrhagia, of whom 14 had endometrial polyps, 40 had uterine fibroids, and 8 had adenomyosis. The VAS score before MEA and 3 and 6 mo after the procedure were 10, 1.3 ± 1.3, and 1.3 ± 1.3, respectively, for menorrhagia and 10, 1.3 ± 1.8, and 1.3 ± 1.8, respectively, for menstrual pain, both showing improvements (P < 0.001). The MEA Hb level significantly improved from 9.2 ± 4.2 g/dL before MEA to 13.4 ± 1.2 g/dL after MEA (P = 0.003). Treatment satisfaction was high, with a VAS score of 9.6 ± 0.7. Endometritis was observed in one patient after surgery and was treated with antibiotics. CONCLUSION: MEA is a safe and effective treatment for menorrhagia.

New native tissue repair for pelvic organ prolapse: Medium-term outcomes of laparoscopic vaginal stump-round ligament fixation.

BACKGROUND: Laparoscopic sacrocolpopexy for pelvic organ prolapse (POP) is a new and widely used approach; however, ever since the United States Food and Drug Administration warned against the use of surgical mesh, repairs performed using patients' tissues [i.e. native tissue repair (NTR)] instead of mesh have attracted much attention. At our hospital, laparoscopic sacrocolpopexy (the Shull method) was introduced in 2017. However, patients with more severe POP who have a long vaginal canal and overextended uterosacral ligaments may not be candidates for this procedure. AIM: To validate a new NTR treatment for POP, we examined patients undergoing laparoscopic vaginal stump-round ligament fixation (the Kakinuma method). METHODS: The study patients were 30 individuals with POP who underwent surgery using the Kakinuma method between January 2020 and December 2021 and who were followed up for > 12 mo after surgery. We retrospectively examined surgical outcomes for surgery duration, blood loss, intraoperative complications, and incidence of recurrence. The Kakinuma method involves round ligament suturing and fixation on both sides, effectively lifting the vaginal stump after laparoscopic hysterectomy. RESULTS: The patients' mean age was 66.5 ± 9.1 (45-82) years, gravidity was 3.1 ± 1.4 (2-7), parity was 2.5 ± 0.6 (2-4) times, and body mass index was 24.5 ± 3.3 (20.9-32.8) kg/m2. According to the POP quantification stage classification, there were 8 patients with stage II, 11 with stage III, and 11 with stage IV. The mean surgery duration was 113.4 ± 22.6 (88-148) min, and the mean blood loss was 26.5 ± 39.7 (10-150) mL. There were no perioperative complications. None of the patients exhibited reduced activities of daily living or cognitive impairment after hospital discharge. No cases of POP recurrence were observed 12 mo after the operation. CONCLUSION: The Kakinuma method, similar to conventional NTR, may be an effective treatment for POP.

Efficacy and safety of an Aron Alpha method in managing giant ovarian tumors.

Background: Giant malignant tumors have an increased risk of intraoperative rupture, which might lead to a worse disease condition and tumor recurrence. We performed a clinical study on patients with a giant ovarian mass who underwent laparoscopy combined with an Aron Alpha method. Methods: This retrospective clinical study spanned from January 2016 to September 2022 and included 23 patients with giant ovarian tumors treated with an Aron Alpha method. Results: The mean age of the subjects was 47.6 ± 17.8 years, mean tumor diameter 20.4 ± 5.8 cm, mean surgical duration 87.2 ± 33.1  min, and mean hemorrhage volume 94.1 ± 92.2 mL. No patient experienced intraoperative tumor rupture or surgery-related symptoms. Histopathology of excised samples revealed serous cyst adenoma and mucinous cystadenoma, mucinous cystadenoma of borderline malignancy and mature cystic teratoma, and endometriotic cyst adenoma in 6, 4, and 3 patients, respectively. The mean hospitalization period was 6.0 ± 1.2 days, and the hospitalization period was not extended in any subject. Conclusion: The Aron Alpha method allows tumor resection without capsular rupture and is a useful, minimally invasive surgical method for resecting giant ovarian tumors in which malignancy cannot be ruled out.

LiNA OperaScopeTM for microwave endometrial ablation for endometrial polyps with heavy menstrual bleeding: A case report.

BACKGROUND: The procedure for microwave endometrial ablation (MEA) follows established MEA practice guidelines but requires hysteroscopic observation of the uterine lumen before and after MEA. When a luminal uterine lesion is recognized, its removal requires preoperative dilation of the cervix because the outer diameter of a conventional rigid hysteroscope is 8.7 mm. Recently, a fully disposable rigid hysteroscope (LiNA OperaScopeTM) with a narrow diameter (4.4 mm) and forceps capable of extracting endometrial lesions has become available. CASE SUMMARY: Here, we report a case of heavy menstrual bleeding (HMB) complicated by endometrial polyps where MEA was performed after removing endometrial polyps using the LiNA OperaScopeTM device. A 48-year-old woman with three prior pregnancies and three deliveries was referred to our hospital for further examination and treatment after being diagnosed with HMB 2 years earlier. The patient underwent MEA following endometrial polypectomy using LiNA OperaScopeTM. After MEA, endometrial cauterization was again examined using the LiNA OperaScopeTM, and the procedure was completed. No preoperative cervical dilation was performed. The patient's clinical course was favorable, and she was discharged 3 h after surgery. One month after surgery, menstruation resumed, and both HMB and dysmenorrhea improved markedly from 10 preoperatively to 1 postoperatively, as assessed subjectively using the visual analog scale. The patient's postoperative course was uneventful with no complications. CONCLUSION: LiNA OperaScopeTM can be a minimally invasive treatment for MEA of HMB with uterine lumen lesions.

Diagnosed corrected transposition of great arteries after cesarean section: A case report.

BACKGROUND: Corrected transposition of the great arteries (cTGA) is a cardiac malformation in which the ventricular and arterial-ventricular positions in the heart are doubly reversed. In general, this defect puts a load on the systemic circulation and causes heart failure, resulting in a poor prognosis. This article reports a case of cTGA detected in a patient with post-caesarean pregnancy who had undergone elective caesarean section and was experiencing an episode of acute heart failure. CASE SUMMARY: This was the case of a 36-year-old gravida 3 para 1 woman. No problems were noted in the puerperal course following the previous pregnancy. The current pregnancy was also uneventful. An elective caesarean section was performed and the patient was discharged from the hospital 7 d after the operation. On postoperative day 18, the patient became aware of breathing difficulty and presented at a nearby clinic, where she was referred to our institution after bilateral pleural effusions were detected. She was then diagnosed with acute heart failure after noting the presence of a prominent pedal oedema and SpO2 91% (supine position and room air); the patient was promptly hospitalised for close examination and treatment. Although chest computed tomography revealed the presence of cTGA, no other cardiac malformations were observed. Owing to improvements in both the pedal oedema and pleural effusions, the patient was discharged on day 9. CONCLUSION: Close examination should be performed on the premise of congenital cardiac malformation when heart failure symptoms are noted during perinatal control.

Prevention and management of hypertrophic scars after laparoscopic surgery using silicone gel sheets: a pilot study.

OBJECTIVE: To assess the effectiveness and safety of modified silicone gel sheets applied to hypertrophic scars and keloids following laparoscopic surgery. METHODS: Patients who had undergone laparoscopic surgery and who had either conventional or modified silicone gel sheets affixed to their surgical lesions for 6 months postoperatively (treatment groups), and control patients who had not received postsurgical treatment involving silicone gel sheets, were enrolled. The surgical wounds were assessed visually and using the Japan Scar Workshop (JSW) Scar Scale. Patients were interviewed before, 3 months after, and 6 months after sheet affixation. RESULTS: A total of 45 patients were included, comprising 15 patients per group. Both silicone gel-sheet groups had significantly lower JSW Scar Scale scores at 3 and 6 months after affixation compared with controls. The scores were not significantly different between the conventional and modified treatment groups and no adverse events were observed in the latter. CONCLUSIONS: Modified silicone gel sheets were more effective than controls and comparable to conventional gel sheets, and there were no adverse events related to laparoscopic surgical wounds in the improved silicone gel sheet group, demonstrating the safety and effectiveness of the modified silicone gel sheets.

Safety and efficacy of manual vacuum aspiration under local anesthesia compared to general anesthesia in the surgical management of miscarriage: a retrospective cohort study.

BACKGROUND: In Japan, dilatation & curettage (D&C) has been performed under general anesthesia as a surgery for an early pregnancy miscarriage for a long time. In 2016, manual vacuum aspiration (MVA) under general anesthesia was introduced at our hospital and has been used as a surgical treatment for first-trimester pregnancy miscarriage, with its utility to date being reported here. In July 2018, our hospital introduced the MVA procedure under local anesthesia. In this study, we evaluated the efficacy and safety of MVA under general and local anesthesia in first-trimester pregnancy miscarriage surgery in Japanese women. METHODS: In this retrospective observational cohort study, we enrolled 322 pregnant women at less than 12 weeks of gestation, who underwent MVA surgery under local anesthesia (n = 166) or conventional general anesthesia (n = 156). The duration of surgery, blood loss volume, quantity of anesthesia, presence or absence of retained products of conception, and clinical complications were evaluated. In addition, the intraoperative pain and treatment satisfaction were assessed using the visual analog scale (VAS). RESULTS: The duration of surgery was significantly shorter in the local anesthesia group. No significant differences were observed between both groups in terms of the blood loss volume and incidence of retained products of conception. In addition, no serious complications were observed in either group. No significant differences were noted between the two groups in the VAS scores for pain and treatment satisfaction. CONCLUSIONS: In this retrospective study, the use of MVA under local anesthesia for early pregnancy miscarriage surgery was found to be equally safe and effective when performed under conventional general anesthesia. This technique allowed the achievement of appropriate pain control with excellent patient satisfaction.

Paclitaxel-carboplatin and bevacizumab combination with maintenance bevacizumab therapy for metastatic, recurrent, and persistent uterine cervical cancer: An open-label multicenter phase II trial (JGOG1079).

OBJECTIVE: This multicenter, open-label, phase II study aimed to evaluate the efficacy and safety of paclitaxel-carboplatin, bevacizumab, and bevacizumab-based maintenance therapy for metastatic, recurrent, and persistent uterine cervical cancer. METHODS: Patients with measurable diseases that were not adapted to regional therapies, such as surgery or radiotherapy, and were systematic chemotherapy-naïve were eligible. The participants received paclitaxel (175 mg/m2), carboplatin (AUC 5), and bevacizumab (15 mg/m2) every three weeks until disease progression or unacceptable adverse events occurred. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall response rate (ORR), overall survival (OS), safety, and time to treatment failure. RESULTS: Sixty-nine patients were analyzed using our protocol. The median paclitaxel- carboplatin therapy duration was six cycles; 40% of patients received bevacizumab maintenance therapy. The median PFS was 11.3 months. The median OS was not reached; the median time to treatment failure was 5.9 months. The ORR was 79.7% [95% confidence interval (CI) 63.8-88.4]; 16 patients (23.2%) showed complete response (CR) and 39 patients (56.5%) showed partial response (PR). The median PFS was 14.3 months (95% CI 7.3-17 months) for the 25 patients who received maintenance therapy and 7.4 months (95% CI 6.1-11 months) for nonrecipients (p = 0.0449). Gastrointestinal perforation/fistulas occurred in four patients (5.6%), all of whom had a history of radiation therapy. CONCLUSIONS: Paclitaxel-carboplatin and bevacizumab therapy is an acceptable and tolerable treatment for advanced or recurrent cervical cancer.

Prognosis and adjuvant chemotherapy for patients with positive peritoneal cytology in stage IA endometrial cancer.

This study evaluated the influence of positive peritoneal cytology (PPC) on the prognosis of patients with stage IA endometrial cancer, and the usefulness of adjuvant chemotherapy in their treatment. We retrospectively analyzed the data of patients with stage IA endometrial cancer admitted in our hospital between 2005 and 2015. Among 989 patients who underwent peritoneal cytology, 135 (13.7%) had PPC. Multivariate analysis extracted several independent risk factors for recurrence in stage IA patients, including those with PPC. Adjuvant chemotherapy did not cause a significant difference in the 5-year relapse-free survival rate in patients with PPC (p = 0.78). Similarly, the 5-year recurrence-free survival rate with or without chemotherapy was not different among type II cancer patients (p = 0.11). However, the baseline risk of 5-year relapse-free survival without chemotherapy in patients with PPC and type II was very low (66.7%). While PPC was an independent risk factor for recurrence in stage IA endometrial cancer, adjuvant chemotherapy did not influence the survival rate in patients with PPC. While it is controversial whether adjuvant chemotherapy should be administered in stage IA uterine cancer with only PPC as a prognostic factor, it should be considered for early-stage patients who have multiple risk factors for recurrence.

Effectiveness of microwave endometrial ablation combined with hysteroscopic transcervical resection in treating submucous uterine myomas.

BACKGROUND: Hypermenorrhea is characterized by excessive menstrual bleeding that causes severe anemia and interferes with everyday life. This condition can restrict women's social activities and decrease their quality of life. Microwave endometrial ablation (MEA) using a 2.45-GHz energy source is a minimally invasive alternative to conventional hysterectomy for treating hypermenorrhea that is resistant to conservative treatment, triggered by systemic disease or medications, or caused by uterine myomas and fibrosis. The popularity of MEA has increased worldwide. Although MEA can safely and effectively treat submucous myomas, some patients may still experience recurrent hypermenorrhea postoperatively and may require additional treatment. AIM: To investigate the efficacy of MEA combined with transcervical resection (TCR). METHODS: Participants underwent cervical and endometrial evaluations. Magnetic resonance imaging and hysteroscopy were performed to evaluate the size and location of the myomas. TCR was performed before MEA using a hystero-resectoscope. MEA was performed using transabdominal ultrasound. The variables included operation time, number of ablation cycles, length of hospital stay, and visual analog scale cores for hypermenorrhea, dysmenorrhea, and treatment satisfaction at 3 and 6 mo postoperatively. The postoperative incidence of amenorrhea, changes in hemoglobin concentrations, and MEA-related complications were evaluated. RESULTS: A total of 34 women underwent a combination of MEA and TCR during the study period. Two patients were excluded from the study as their histopathological tests identified uterine malignancies (uterine sarcoma and endometrial cancer). The 32 eligible women (6 nulliparous, 26 multiparous) had a mean age of 45.2 ± 4.3 years (range: 36-52 years). Patients reported very severe hypermenorrhea (10/10 points on the visual analog scale) before the procedure. However, after the procedure, the hypermenorrhea scores decreased to 1.2 ± 1.3 and 0.9 ± 1.3 at 3 and 6 mo, respectively (P < 0.001). The mean follow-up duration was 33.8 ± 16.8 mo. Although 10 women (31.3%) developed amenorrhea during this period, none experienced a recurrence of hypermenorrhea. No surgical complications were observed. CONCLUSION: Reducing the size of uterine myomas by combining MEA and TCR can safely and effectively treat hypermenorrhea in patients with submucous myomas.

Efficacy and safety of standard of care with/without bevacizumab for platinum-resistant ovarian/fallopian tube/peritoneal cancer previously treated with bevacizumab: The Japanese Gynecologic Oncology Group study JGOG3023.

We investigated the efficacy and safety of further bevacizumab therapy in patients with platinum-resistant ovarian cancer whose disease had progressed after bevacizumab plus chemotherapy. In this multicenter, open-label, phase II trial (JGOG3023), patients were randomized 1:1 to a single-agent chemotherapy alone (either pegylated liposomal doxorubicin [40 or 50 mg/m2 administered intravenously], topotecan [1.25 mg/m2 intravenously], paclitaxel [80 mg/m2 intravenously], or gemcitabine [1000 mg/m2 intravenously]) or single-agent chemotherapy + bevacizumab (15 mg/m2 intravenously). The primary endpoint was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary endpoints were overall survival (OS), objective response rate (ORR), and response rate according to Gynecological Cancer Intergroup cancer antigen 125 criteria. In total, 103 patients were allocated to chemotherapy (n = 51) or chemotherapy + bevacizumab (n = 52). Median investigator-assessed PFS was 3.1 and 4.0 mo in each group, respectively (hazard ratio [HR] = 0.54, 95% confidence interval [CI]: 0.32-0.90, P = .0082). Median OS was 11.3 and 15.3 mo in each group, respectively (HR = 0.67, 95% CI: 0.38-1.17, P = .1556). Respective ORRs were 13.7% and 25.0% (P = .0599) and response rates were 16.7% and 21.4% (P = .8273). The incidence of grade ≥3 treatment-related AEs was 42.0% in the chemotherapy group and 54.9% in the chemotherapy + bevacizumab group; AEs were well tolerated, with only 2 and 12 events leading to discontinuation of therapy, respectively. Bevacizumab was effective beyond progressive disease and AEs were manageable. The observed improvement in PFS requires further verification.

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA).

PURPOSE: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.

Phase 2 single-arm study on the safety of maintenance niraparib in Japanese patients with platinum-sensitive relapsed ovarian cancer.

OBJECTIVE: The primary objective of this study was to evaluate the safety of niraparib 300 mg/day in Japanese patients with platinum-sensitive, relapsed ovarian cancer in a maintenance setting. METHODS: Phase 2, multicenter, open-label, single-arm study enrolled Japanese patients with platinum-sensitive, relapsed ovarian cancer who had received ≥2 platinum-based regimens. The primary endpoint (incidence of grade 3 or 4 thrombocytopenia-related events within 30 days after initial niraparib administration) was justified by the incidences of a global pivotal phase 3 study and its post-hoc safety analysis on thrombocytopenia, the major hematological adverse event of niraparib. The overall safety analysis examined other treatment-emergent adverse events (TEAEs). RESULTS: Enrolled patients (n=19) had a median (min, max) body weight of 53.9 (40.8-79.1) kg; all but one patient weighed <77 kg. Most (94.7%) patients initially received niraparib 300 mg/day but this decreased in subsequent cycles (mean±standard deviation dose intensity, 191.6±65.7 mg/day). In total, 6/19 (31.6%) patients experienced grade 3 or 4 thrombocytopenia-related events within 30 days of initial niraparib administration. Other common TEAEs included nausea, and decreased platelet or neutrophil counts. No progression-free or overall survival events occurred; only 1 of 4 response-evaluable patients had a post-baseline tumor assessment (stable disease). CONCLUSION: The incidence of grade 3 or 4 thrombocytopenia-related events in Japanese ovarian cancer patients was similar to that in the corresponding non-Japanese study. Overall, the safety profile was acceptable and consistent with the known safety profile and previous experience with niraparib. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759587.

A retrospective assessment of the safety and efficacy of laparoscopic radical hysterectomy in Japan during the early years following its introduction: a Japanese Gynecologic Oncology Group study (JGOG1081S).

OBJECTIVE: To evaluate the safety and efficacy of laparoscopic radical hysterectomy (LRH) for cervical cancer, in terms of morbidity and short-term oncologic outcome following LRH's introduction into Japan. METHODS: We conducted a retrospective analysis of patients with early-stage cervical cancer (FIGO staging IA2, IB1, and IIA1) who underwent LRH from Dec 2014 to Dec 2016. We assessed the morbidity, overall survival (OS) and recurrence-free survival (RFS), and prognostic factors for RFS. RESULTS: A total of 251 patients were included from 22 facilities across Japan. There were 8 cases of stage IA2 cervical cancer, 226 of IB1, and 17 of IIA1. The median operating time was 343 min and the median blood loss was 190 ml. Two patients (0.8%) had a postoperative complication with a Clavien-Dindo classification of grade 3 or higher. After a median follow-up time of 15.6 months, the 2-year RFS was 87.4%, and the 2-year OS was 97.8%. When the 2-year RFS rate was compared with whether the patient pathologically had tumors of less than 2 cm, versus 2 cm or more, the RFS was 95.8% and 80.4%, respectively. Multivariate analysis found that tumor size and the route of lymph node removal were independent prognostic factors for recurrence. CONCLUSION: When LRH was first introduced into Japan, we found that the route of lymph node removal was an independent prognostic factor for recurrence in addition to large tumors (≥ 2 cm). Our results suggest that prognosis may be secured by paying attention to the lymph node removal route.

Continuous Administration of Bevacizumab After Disease Progression in Recurrent Ovarian Cancer: A Retrospective Observational Study.

BACKGROUND/AIM: Chemotherapy with additional bevacizumab is the standard treatment for primary and recurrent ovarian cancer. We aimed to investigate the clinical utility and safety of bevacizumab when used in combination with chemotherapy after disease progression. PATIENTS AND METHODS: This retrospective, observational study recruited patients treated for recurrent ovarian cancer from 2014 to 2016. We evaluated the effects of bevacizumab with chemotherapy in patients whose disease had progressed following treatment with bevacizumab. We assessed progression-free survival and adverse events. RESULTS: Thirty-three patients received post-progression treatment with bevacizumab. The median progression-free survival was 8.7 months (95% confidence interval=5.5-11). The progression-free survival was compared pre- and post-progression treatment, and was longer in platinum-resistant than platinum-sensitive cases after treatment (p=0.06). The most common non-hematological toxicity was proteinuria. The incidence of serious adverse events was low. CONCLUSION: Continuous administration of bevacizumab may be beneficial for ovarian cancer patients after disease progression.